Glucocorticoid receptor in human placenta: Studies of concentration and functional differences of preterm and term tissue

Glucocorticoids have been suspected of being a factor in premature parturition. This study identifies and characterizes a glucocorticoid receptor in human placentas at various gestational ages. Placental segments in culture translocate ³H-labeled steroid to the nucleus. Scatchard analysis of placental cytosol reveals a relatively high-affinity (dissociation constant = 10^-8) and low-capacity binding of dexamethasone to a protein. An 8S-to-4S shift with low-to-high salt treatments is shown by sucrose density gradient analysis. The binding protein is precipitated by 35% ammonium sulfate. This ammonium sulfate fraction of cytosol displays a steroid specificity and a capacity of the receptor to bind to nuclear acceptor sites in cell-free assays. Thus, the presence of a glucocorticoid receptor is supported. A sevenfold to twelvefold increase in concentration of receptor was found between samples of placental tissue from the first and second trimesters; no significant difference was detected between the second and third trimesters. The capacities of the "receptors" from mature and premature placental tissues to bind to chromatin were not markedly different; thus, the biologic activities of the receptors among the different trimesters appear equivalent. The placenta thus appears to be a target tissue for glucocorticoids. The pronounced differences in receptor concentrations in placentas from different trimesters may reflect differential responsiveness of the organ to the systemic steroid.